To facilitate the study of molecular evolution and understand the origins and evolution of new genetic systems at the molecular level, two mutually related research projects are proposed. The first project is for developing new statistical methods and efficient computer programs that can handle large-scale molecular data from the evolutionary point of view. Special efforts will be made to develop an efficient method of constructing neighbor joining trees for hundreds or thousands of sequences and update our computer program package MEGA: molecular evolutionary genetics analysis The second project is for studying the mechanism of evolution of multigene families arid the origins of new genes and new genetic systems that are important for biological adaptation. In the next grant period we will focus on the evolution of the primate KIR and the rodent Ly49 gene families encoding natural killer cell receptors as a model genetic system that has evolved rapidly in recent years and the MADS-box gene family controlling flower development and developmental processes in plants, fungi, and animals as a model genetic system that has evolved very slowly but generated several important new genetic systems. We are also interested in studying the largest vertebrate gene family of olfactory receptors composed of 100 to 1000 member genes. This study is expected to give important information on the molecular mechanism of gene duplication, gene death, inter chromosomal gene transfer, etc. and evolution of various forms of olfaction in terrestrial and aquatic vertebrates. In these studies, most DNA and protein sequences to be used will be obtained by homology search from the genome sequences of various model organisms.